Valacyclovir is an amino acid derivative of the acyclovir which is an acyclic analog of natural nucleoside guanine. Acyclovir shows selective and strong antiviral activity, especially against herpes simplex viruses.
Acyclovir lacks 3′-hydroxyl group at the side chain and so terminates chain elongation step of the viral DNA during DNA replication. See, Goodman et al, in The Pharmacological Basis of Therapeutics 1193-1198 (9th ed. 1996). The chemical name of the acyclovir is 2-Amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one] and the CAS Registry number is 59277-89-3. Formula I shows the chemical structure of acyclovir.

The chemical name of the valacyclovir hydrochloride is L-Valine 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy]ethyl ester hydrochloride and the CAS Registry number is 124832-26-4. Formula II shows the chemical structure of valacyclovir hydrochloride.

Although acyclovir shows strong antiviral activity (Schaeffer et al, Nature 1978, 272, 583), it is poorly absorbed from the gastrointestinal track. Because of this low bioavailability of acyclovir, multiple high doses of the oral drug must be taken.
However α-amino group of the valacyclovir can form hydrochloride salt and this increases the solubility and bioavailability of the drug without loosing its antiviral activity (see, for example U.S. Pat. No. 4,957,924 ).
Valacyclovir hydrochloride is prepared following the basic patent EP 0308 065. Preparation of an anhydrous form of valacyclovir hydrochloride is described in U.S. Pat. No. 6,107,302. In another patent application (WO 03/022209 A2) more polymorphs of the antiviral valacyclovir hydrochloride are reported.
Discovery of the new crystalline forms of the active pharmaceuticals provides new possibilities for the formulation studies and can increase the stability of the active ingredients.